We propose to use a new method to describe the distributions of ventilation-perfusion ratios in patients with a variety of lung diseases. The method is based on the elimination of a series of infused inert gases having a range of solubilities. This method has already been shown to work well in dogs and normal human volunteers. We shall study the effects of oxygen breathing on the distribution of ventilation-perfusion ratios since this has already been shown to exaggerate the amount of shunted blood. The patients to be studied include those with chronic obstructive lung disease where we shall make special efforts to study those with pure emphysema and pure chronic bronchitis. Measurements will also be made on patients with bronchial asthma before and after bronchodilator therapy, and patients with interstitial lung disease. Patients with acute respiratory failure will be studied in the intensive care setting and we shall determine the effects of positive end-expiratory pressure (PEEP) on the distributions of ventilation-perfusion ratios. These investigations on patients will be supplemented by experiments on anesthetized dogs in which respiratory failure will be induced by oleic acid infusions or the injection of microemboli. We expect that this research will contribute to our understanding of the basic mechanisms of the impairment of gas exchange in various types of lung disease, and also help in improving the management of these patients, especially those in the intensive care setting.